Our study demonstrates that tertiary lymphoid structure (TLS)-related genes play a crucial role in neuroblastoma (NB) prognosis, with a 6-gene TLS signature (CCL2, CCL4, CCL21, CD200, CXCR3, and IGSF6) serving as a promising prognostic biomarker for NB. This evidence concerns the gene IGSF6 and neuroblastoma.